The invention relates to the use of extracts of Ginkgo biloba for preparing a medicament intended to treat amyotrophic lateral sclerosis (ALS).
It is already known that extracts of Ginkgo biloba have an activity in the cardiovascular field (in particular the reduction of platelet adhesion), in the central nervous field (in particular a neuroprotective activity) or in the neurosensory system (in particular retinal protection); cf. for example DeFeudis et al., Ginkgo Biloba Extract (EGb 761), Pharmaceutical Activities and Clinical Applications (Elsevier, Paris, 1991). Their preparation has been the subject of a certain number of patents, of which there can be mentioned the European Patents EP 431 535 and EP 431 536, and the American Patent U.S. Pat. No. 5,389,370.
Certain products can be used in the treatment of ALS. In particular there can be mentioned riluzole, gabapentin, 1-(2-naphth-2-ylethyl)-4-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyridine or vitamin E (cf. Gurney M. E. et al., Ann. Neurol., 39 (1996), 147-157; Patent Application PCT WO 97/15304).
Now the Applicant has just found that certain extracts of Ginkgo biloba also have useful new pharmacological properties, namely retarding and attenuating the symptoms of ALS. In particular, the Applicant was able to note the beneficial effects of these extracts on genetically modified mice suffering from ALS.
Therefore a subject of the invention is the use of these extracts for preparing a medicament intended to treat ALS.
By extract of Ginkgo biloba is understood at least one of the individual compounds which can be obtained by extraction from the Ginkgo biloba L. tree, and in particular a flavonoid compound or a terpene such as a ginkgolide or a bilobalide, or also a mixture of the latter. Preferably, the extract used will be such that it contains an effective quantity of ginkgolides. For the uses according to the invention, an extract of type EGb 761 or CP 401 can for example be chosen.
By ginkgolide is understood all the natural ginkgolides obtained from the Ginkgo biloba tree, as well as synthetic ginkgolides and their derivatives (resulting for example from an acetylation or alkoxylation reaction) and pharmaceutically active salts. The ginkgolides used can for example be ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J or ginkgolide M (structures given in the diagram below; these compounds can be isolated from extracts of Ginkgo biloba leavesxe2x80x94see GINKGOLIDES, Chemistry, Biology, Pharmacology and Clinical Perspectives, published by P. Braquet, J. R. Prous Science Publishers, in particular Volumes 1 (1988) and 2 (1989)). Glycosylated derivatives of ginkgolides or alkoxylated or acetylated derivatives of ginkgolides can also be used (cf. Weber, M. and Vasella, A., Helv. Chim. Acta, 80 (1997) 2352-2367). By alkoxylated derivative of ginkgolide is understood a ginkgolide derivative comprising at least one linear or branched alkoxy group, instead of a hydroxy group (these compounds are described in French Patent Application No. FR 88.14392). Similarly, by acetylated derivative of ginkgolide is understood a derivative of ginkgolide comprising at least one acetate group instead of a hydroxy group.
By extract of type EGb 761 is understood an extract of a composition substantially identical to that of the standardized extract EGb 761 as defined in particular in the following article: K. Drieu, La presse medicale, 31, Sep. 25, 1986, supplement devoted to the extract of Ginkgo biloba (EGb 761), 1455-1457; or in the European Patents EP 431 535 and EP 431 536; by extract of type EGb 761 is therefore understood in particular extracts of Ginkgo biloba comprising 20 to 30% of flavoneglycosides, 2.5 to 4.5% of ginkgolides A, B, C and J, 2 to 4% of bilobalide, less than 10% of proanthocyanidines and less than 10 ppm, and preferably less than 5 ppm, of compounds of alkylphenol type, and in particular extracts of Ginkgo biloba comprising approximately 24% of flavoneglycosides, 3.1% of ginkgolides A, B, C and J, 2.9% of bilobalide, 6.5% of proanthocyanidines and less than 1 ppm of compounds of alkylphenol type. By extract of type CP 401 is understood extracts such as those which are presented in the U.S. Pat. No. 5,389,370, in particular extracts of Ginkgo biloba containing 5.5 to 8% of ginkgolides A, B, C and J, 40 to 60% of flavoneglycosides and 5 to 7% of bilobalide, and quite particularly extracts containing approximately 7% of ginkgolides A, B, C and J, 50% of flavoneglycosides and 6% of bilobalide.
The invention also relates to the use of a compound of general formula (I) 
in which W, X, Y and Z represent independently the H, OH, linear or branched alkoxy or O-GS radicals, GS-OH representing a mono- or a disaccharide, or one of their derivatives or analogues, it being understood that at least one of W, X, Y or Z represents an O-GS radical, for preparing a medicament intended to treat ALS.
The invention preferably relates to the use of a compound of general formula (I) 
in which X represents an OH or O-GS radical, GS-OH representing a mono- or a disaccharide, or one of their derivatives or analogues, and:
either W represents an OH or O-GS radical, Y represents H and Z represents H;
or W represents an OH or O-GS radical, Y represents an OH or O-GS radical and Z represents H;
or W represents an OH or O-GS radical, Y represents an OH or O-GS radical and Z represents an OH or O-GS radical;
or W represents an OH or O-GS radical, Y represents H and Z represents an OH or O-GS radical;
or W represents H, Y represents an OH or O-GS radical and Z represents an OH or O-GS radical;
or W represents an OH or O-GS radical, Y represents a linear or branched alkoxy radical and Z represents H;
it being understood that at least one of W, X, Y or Z represents an O-GS radical, for preparing a medicament intended to treat ALS.
The invention quite particularly relates to the use of a compound of general formula (I) 
in which X represents an OH or O-GS radical, GS-OH representing a mono- or a disaccharide, or one of their derivatives or analogues, and:
either W represents an OH or O-GS radical, Y represents H and Z represents H;
or W represents an OH or O-GS radical, Y represents an OH or O-GS radical and Z represents H;
or W represents an OH or O-GS radical, Y represents a linear or branched alkoxy radical and Z represents H;
it being understood that at least one of W, X, Y or Z represents an O-GS radical, for preparing a medicament intended to treat ALS.
By linear or branched alkoxy radical, is understood in the present description an alkoxy radical the linear or branched carbon-containing chain of which, contains 1 to 6 carbon atoms. By derivative or analogue of mono- or disaccharides, is understood compounds such as N-acetylglucosamine, N-acetylalosamine, galactosamine, mannoseamine, N-tosylhydrazone, etc.
Preferably, O-GS will be chosen so that GS-OH belongs to the group comprising abequose, rhamnose, arabinose, ribose, xylose, 2-deoxyribose, glucose, galactose, mannose, 2-deoxyglucose, fructose, fucose, N-acetylglucosamine, N-acetylalosamine, galactosamine, mannosamine, saccharose, lactose, maltose, cellobiose and trehalose. Yet more preferably, O-GS will be chosen so that GS-OH belongs to the group comprising glucose and lactose.
The different processes for obtaining the glycolsylated derivatives of ginkgolides or alkoxylated ginkgolides (i.e. those resulting from a glycosylation reaction carried out on at least one of the OH groups of the ginkgolides or of their alkoxylated derivatives) are described in the following publication: Weber, M. and Vasella, A., Helv. Chim. Acta, 80 (1997), 2352-2367.